Aggresomes do not represent a general cellular response to protein misfolding in mammalian cells.
BACKGROUND
Aggresomes are juxtanuclear inclusion bodies that have been proposed to represent a general cellular response to misfolded proteins in mammalian cells. Yet, why aggresomes are not a pathological characteristic of protein misfolding diseases is unclear. Here, we investigate if a misfolded protein inevitably forms aggresomes in mammalian cells.


RESULTS
We show that a cytoplasmic form of the prion protein may form aggresomes or dispersed aggregates in different cell lines. In contrast to aggresomes, the formation of dispersed aggregates is insensitive to histone deacetylase 6 inhibitors and does not result in cytoskeleton rearrangements. Modulation of expression levels or proteasome inhibitors does not alter the formation of dispersed aggregates.


CONCLUSIONS
Our results establish that aggresomes are not obligatory products of protein misfolding in vivo.
Beaudoin
Simon
S
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada. simon.beaudoin@usherbrooke.ca
Goggin
Kevin
K
Bissonnette
Cyntia
C
Grenier
Catherine
C
Roucou
Xavier
X
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D002479:Inclusion Bodies / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D011328:Prions / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding
D011328:Prions